Frequency and clinical outcomes of flares related to nucleos(t)ide analogue therapy in patients with chronic hepatitis B.

Flares in chronic hepatitis B are often detrimental but sometimes lead to sustained immune control and disease remission. The aim of this study was to estimate the frequency of hepatitis flares which occur during and/or after cessation of nucleos(t)ide analogue (NA) therapy, and to assess their outcomes. In a single centre cohort study we investigated 227 patients who received a total of 351 NA treatment courses. NA therapy was discontinued after 149 treatment courses. In total, 27 flares were observed during 9779 on-treatment patient-months. The frequency was estimated as 3.2 per 100 person-years (95% CI 2.2-4.7). Lamivudine (LAM)-treated patients demonstrated the highest frequency (4.9/100 person-years, 95% CI 3.2-7.4). Twenty (74%) of 27 on-therapy flares were associated with development of genotypic resistance, which all occurred during LAM therapy. NA withdrawal flares occurred after a median post-treatment follow-up of 3.5 months in 17 (11%) of 149 treatment discontinuations. No flares were observed in patients who switched to another antiviral agent (n = 51). None of the on-therapy and withdrawal flares related to NA therapy were associated with sustained disease remission, and seven flares resulted in decompensated liver disease. In this study, flares related to NA therapy never led to immune control and sustained disease remission, and sometimes resulted in decompensated liver disease.

[Development of the medical treatment of diabetes in Luxembourg]. / Evolution du traitement médicamenteux du diabète au Luxembourg.

OBJECTIVES: The aims of the study were to estimate the prevalence of diabetes in Luxembourg in 2002, to compare it to the prevalence reported in 1991 and to evaluate if prescription attitudes have changed since 1991. METHODS: The prevalence of diabetes was estimated using the drug sales data. The key parameters, total amount of antidiabetic drugs sold in one year and the average daily dose or Prescribed Daily Dose (PDD), have been obtained from the National Social Security Organization and by a standardized questionnaire sent to all general practitioners and all internists and endocrinologists of the country. RESULTS: The PDD was calculated on 2,402 questionnaires on individual diabetic patients. By this mean, the proportion of patients only treated with appropriate diet could also be obtained. Compared to 1991, the total amount of antidiabetic drugs showed a four-fold increase in biguanides tablet prescriptions. A high percentage of combined treatments was found. The prevalence of diabetes in Luxembourg was found to be 3.05% of the total population. CONCLUSIONS: Compared to the status in 1991, prevalence of diabetes increased by 63%, which seems mainly due to type 2 diabetic patients as orally-treated diabetic patients almost doubled (2.11% vs 1.16%). A substantial change in prescriptions for diabetes has occurred, suggesting a positive influence of studies like the United Kingdom Prospective Diabetes Study (UKPDS).

Changes in diabetes prevalence and treatment in the last ten years in Luxembourg. A lesson from the United Kingdom prospective diabetes study?

OBJECTIVES: The aims of the study were to estimate the prevalence of diabetes in Luxembourg in 2002, to compare it to the prevalence reported in 1991 and to evaluate if prescription attitudes have changed since 1991. METHODS: The prevalence of diabetes was estimated using the drug sales data. The key parameters, total amount of antidiabetic drugs sold in one year and the average daily dose or Prescribed Daily Dose (PDD), have been obtained from the National Social Security Organization and by a standardized questionnaire sent to all general practitioners and all internists and endocrinologists of the country. RESULTS: The PDD was calculated on 2, 402 questionnaires on individual diabetic patients. By this means, the proportion of patients only treated with appropriate diet could also be obtained. Compared to 1991, the total amount of antidiabetic drugs showed a four-fold increase in metformine tablet prescriptions. A high percentage of combined treatments was found. The prevalence of diabetes in Luxembourg was found to be 3.05% of the total population. CONCLUSIONS: Compared to the status in 1991, prevalence of diabetes increased by 63%, which seems mainly due to type 2 diabetic patients as orally-treated diabetic patients almost doubled (2.11% vs 1.16%). A substantial change in prescriptions for diabetes has occurred, suggesting a positive influence of studies like the United Kingdom Prospective Diabetes Study (UKPDS).

The glutathione-related detoxification system is increased in human breast cancer in correlation with clinical and histopathological features.

PURPOSE: The glutathione detoxification pathway includes glutathione S-transferase (GST) and peroxidase (GPX) isoenzymes as well as glutathione reductase (GSSR). Though well established from cultured cancer cell lines, its involvement in resistance is still unclear in the tumours. This study aimed to describe the parameters that influence the glutathione contents and associated activities in breast cancer. METHODS: The components of the glutathione pathway were measured in the tumours from 41 women with primary breast cancer in comparison with those in the matched tumour-free samples. Appropriate statistical studies (regression analysis, Wilcoxon signed rank test) explored the influence of clinical and prognostic factors. RESULTS: Reduced and total glutathione contents were largely increased (P < 0.0001) and all related activities were significantly enhanced in the tumours. Interindividual variations were described, probably due to various parameters (age, menopause, axillary lymph node status, S and G2 + M cell fractions, ER, cathepsin-D and c-ErbB-2 expressions) that influence particular components of the glutathione pathway, especially the glutathione levels. CONCLUSIONS: The breast tumours improved their redox status and detoxification capacities depending on various parameters of significance for cell proliferation and aggressiveness, which supports the involvement of the glutathione pathway in malignant cell resistance to oxidative stress and apoptosis.

The glutathione-related detoxification pathway in the human breast: a highly coordinated system disrupted in the tumour tissues.

Glutathione and the associated enzymes, glutathione S-transferases, peroxidases, and reductase, have been implicated in cancer chemoresistance. This pathway was investigated in paired cancerous and peritumoral breast samples from 41 women. The tumours exhibited a higher redox status as deduced from increased transferase, peroxidase, and reductase activities and from higher total and reduced glutathione contents. Several components were strongly correlated in peritumoral tissues, suggesting a highly co-ordinated glutathione pathway that appeared disrupted in breast tumours with only a few correlations left. Therefore, resistance could spontaneously result from deregulated variations in the glutathione pathway, which might be relevant to the malignant disease progression.

Anti-Hu antibody titre and brain metastases before and after treatment for small cell lung cancer.

OBJECTIVES: To follow up the level of anti-Hu antibody titres during chemotherapy and to compare the pattern of metastases and other neurological complications before and after chemotherapy in patients with small cell lung cancer (SCLC) with and without low titre anti-Hu antibodies. Seventeen per cent of patients with SCLC without paraneoplastic syndromes have a low titre of anti-Hu antibodies in their serum. Previous studies suggested that these antibodies correlate with a more indolent tumour growth. METHODS: The serum of 52 consecutive patients with SCLC were studied before and during chemotherapy, and the correlation with stage of disease and pattern of metastases was examined. All serum samples were investigated using western blot and enzyme linked immunosorbent assay (ELISA) with HuD recombinant protein. All patients with SCLC were investigated using MRI of the brain, CSF, bone marrow aspiration, ultrasound of the abdomen, and radionuclide bone scan. RESULTS: Nine (17%) of 52 SCLC serum samples were positive by western blot. At the time of diagnosis none of the anti-Hu positive patients had either CNS (brain or leptomeningeal), epidural, adrenal, or bone marrow metastases and 56% had limited disease. In eight of 43 anti-Hu negative patients CNS metastases were found at the time of diagnosis, and only 30% had limited disease. The prevalence of bone and liver metastases was similar in both groups. Survival was 11 (SD ) months for the 43 anti-Hu negative and 10 (SD 6) months for the nine anti-Hu positive patients. Male:female ratio in the anti-Hu negative group was 4.4:1, and in the anti-Hu positive group 2:1. CONCLUSIONS: No anti-Hu antibody positive serum, as tested by western blot, became negative during chemotherapy. Anti-Hu positive and anti-Hu negative patients had similar survival, but anti-Hu positive patients tended to be women, had limited disease at the time of tumour diagnosis, and initially metastases seemed to spare the nervous system.

The generation of new S alleles at the incompatibility locus of Lycopersicum peruvianum Mill.

A detailed analysis has been made of S genotypes in progenies derived from induced and spontaneous inbreeding processes in a clonal population of Lycopersicum peruvianum Mill. The results indicate that, in certain genetic backgrounds, induced inbreeding leads to the generation of a new S allele which usually first appears in the pistil of individuals otherwise homozygous for one of the parental specificities. When the change in specificity occurs in S heterozygotes, spontaneous self-compatibility is promoted and the new allele can be transmitted, via selfing, to the following generation.The factors and mechanisms which may be involved in the generation of new specificities at the S locus of higher plants are discussed and preliminary evidence is provided which suggests that the hypothesis of mutation by equal crossing-over is not applicable to the present study.